The long-term goal of this research program is characterize the manner, mechanisms and site(s) of action by which the neurointermediate pituitary lobe (NIL) influences the secretion of adrenocorticotropin (ACTH) and prolactin (PRL) from the anterior pituitary (AP). Recent studies demonstrate that the surgical removal of the NIL in vivo (NIL-X) significantly and selectively influences the dynamic secretion of ACTH and PRL from the AP. However, very little is known concerning the factor(s), mechanisms(s) and site(s) of action by which this influence of the NIL on AP hormone secretion is exerted. The present proposal will test the hypothesis that the NIL influences ACTH and PRL secretion both by modifying the sensitivity of the AP to respond to known, physiologically relevant releasing-(RF) and release-inhibiting factors (RIF) for the hormones, ACTH and PRL, and by interacting with the brain in a feedback manner to regulate the concentrations and release of RF/RIF involved in ACTH and PRL secretion. The in vivo ACTH and PRL secretory responses to RF/RIF will be evaluated at acute (16 hr) and intermediate (12 day) and chronic (28 days) time points following NIL-X or sham operations in freely moving, unanesthetized rats. The ability of NIL-X to affect the concentrations, synthesis, and release of physiologically relevant RF/RIF in the brain will be evaluated using specific radioimmunoassays, in situ hybridization techniques, and HPLC coupled with electrochemical detection. In addition, if the sensitivity of the AP hormonal response to RF/RIF stimulus or the concentration/synthesis/release of central RF/RIF is determined to be altered by NIL-X, then additional studies will examine which of these NIL-X induced effects are due to the removal of oxytocin (OXY) and/or arginine- vasopressin (AVP) secreting nerve terminals located within the NIL: the ability of replacement therapy with OXY and/or AVP to reverse the NIL-X- induced effects as well as the ability of chronic treatment with potent AVP and/or OXY antagonists to induce changes, similar to those observed following NIL-X will be examined. The knowledge gained from these studies should not only advance greatly our basic scientific knowledge concerning the neuroendocrine regulation of ACTH and PRL secretion from the AP, but should also permit the development of dynamic tests to characterize and diagnose the nature of underlying causes responsible for the abnormal secretion of ACTH and PRL, and provide insight toward the development of possible novel therapeutic regimens for the alleviation of clinical dysfunction resulting from the abnormal secretion of ACTH and PRL.